Pacritinib to Inhibit JAK/STAT Signaling in Refractory Colorectal Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed refractory colorectal cancer

- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by
chest x-ray, or >10 mm with calipers by clinical exam.

- Refractory to or intolerant of standard systemic therapy, including having received
two or more standard available therapies known to prolong survival for which s/he was
eligible, including FOLFOX or FOLFIRI with or without bevacizumab, aflibercept,
cetuximab, or panitumumab

- At least 18 years of age.

- ECOG performance status < 2

- Life expectancy ≥ 12 weeks.

- Normal bone marrow and organ function as defined below:

- Absolute neutrophil count ≥ 1,500/mcl

- Platelets ≥ 50,000/mcl

- Total bilirubin ≤ 2.0 x IULN

- AST (SGOT) / ALT (SGPT) ≤ 3.0 x IULN

- Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance > 60 mL/min/1.73 m2 for
patients with creatinine levels above 2.0 mg/dL

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry
and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she must inform her
treating physician immediately.

- Able to understand and willing to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- Prior therapy with a JAK2 or FLT3 inhibitor.

- A history of other malignancy ≤ 5 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only or
carcinoma in situ of the cervix.

- Received any chemotherapeutic or targeted agent for metastatic colorectal cancer
within two weeks of initiation of study drug.

- Currently receiving any other investigational agents.

- Known brain metastases. Patients with known brain metastases must be excluded from
this clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to pacritinib or other agents used in the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14
days of study entry.

- Known HIV-positivity on combination antiretroviral therapy because of the potential
for pharmacokinetic interactions with pacritinib. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.

- Use of potent cytochrome P450 3A4 (CYP3A4) inhibitor within one week of pacritinib
initiation.

- Patients with CTCAE grade 2 cardiac arrhythmias may be considered for inclusion if
the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety.
Patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade ≥
3, corrected QT interval (QTc) prolongation >450ms, or other factors that increase
the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as
serum potassium <3.0mEq/L that is persistent and refractory to correction], or family
history of long QT interval syndrome).

- Any gastrointestinal (GI) or metabolic condition that could interfere with absorption
of oral medication such as ongoing grade 3 or higher diarrhea, constipation, nausea,
or vomiting.

- Active viral hepatitis.